Pyridine → Tert-butyl 4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)-4-(2-methoxyethoxy)piperidine-1-carboxylate

HRID 216087Notes

Reaction equation

HRID 216087 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([O:17][CH2:18][CH2:19][O:20][CH3:21])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[CH3:34][N:35]([CH3:46])[C:36](=[O:45])[O:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([NH2:44])[CH:39]=1>CN(C=O)C.C(Cl)Cl>[CH3:34][N:35]([CH3:46])[C:36]([O:37][C:38]1[CH:39]=[C:40]([NH:44][C:14]([C:11]2([O:17][CH2:18][CH2:19][O:20][CH3:21])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[O:16])[CH:41]=[CH:42][CH:43]=1)=[O:45]

Participants

7

Reactant 4

HCID 1049PyridineHCID 298773-Aminophenyl dimethylcarbamateHCID 65578Oxalyl chlorideHCID 670367781-(Tert-butoxycarbonyl)-4-(2-methoxyethoxy)piperidine-4-carboxylic acid

Product 1

HCID 67036832Tert-butyl 4-(3-(dimethylcarbamoyloxy)phenylcarbamoyl)-4-(2-methoxyethoxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of carboxylic acids from step B, pyridine (0.2 mL, 2.48 mmol), and DMF (catalytic, 2 drops) in CH2Cl2 (3.1 mL) was added dropwise oxalyl chloride (60 μL, 0.68 mmol, caution: exothermic). After gas evolution subsided, the reaction was stirred at ambient temperature for 30 minutes. 3-Aminophenyl dimethylcarbamate (112 mg, 0.62 mmol) was added in one portion to this solution, which was stirred for another 30 minutes. The reaction was quenched with saturated aq. NH4Cl, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried with MgSO4, filtered, and concentrated under vacuum. Silica gel chromatography (80% ethyl acetate:hexanes) afforded the title compound as an off-white solid (150 mg). MS (ES+) [M+CH3CN]+=529.3.

Workup

  1. stirringwas stirred for another 30 minutes
  2. customThe reaction was quenched with saturated aq. NH4Cl
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-be8ed48330cb40a5986e3afa4b1b6d46
Source dataset
uspto-grants-2012_06
Patent number
US08193202B2

Reaction notes

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